A novel multi-lineage human intestinal organoid screening platform for drug discovery and preclinical testing

Intero Biosystems Inc. received a $349,952 Project Grant from the National Center for Advancing Translational Sciences (NCATS, CFDA 93.350) awarded on June 20, 2025, with a completion date of June 19, 2026. In collaboration with the University of Michigan, the awardee is developing and validating a novel stem cell-derived human intestinal organoid (HIO) screening platform designed to improve preclinical drug testing and reduce the current 90% failure rate of drug candidates in clinical trials. The HIO system mimics native intestinal physiology by incorporating multiple tissue types, including the intestinal epithelium, functional smooth muscle capable of peristalsis, perfusable blood vessels, and neurons.

The project deliverables include optimization and validation of the HIO system for standard cytotoxicity and cell viability assays commonly used in preclinical drug screening, as well as development of an intestinal fibrosis disease model for drug efficacy testing. The awardee will induce fibrosis through transforming growth factor beta (TGFβ) addition and develop a scalable quantitative polymerase chain reaction (qPCR) panel to assess fibrotic induction. Upon completion, these outputs will position human intestinal organoids as a powerful microphysiological system capable of revolutionizing preclinical drug discovery and development processes.

Abstract

The drug development pipeline currently tests drug candidates on simple cell monolayers or animal models; however, 90% of new drugs fail clinical trials, wasting millions of dollars and leaving patients in need. There is an urgent need for better models of human physiology that can accurately mimic the toxicity and efficacy of drug candidates in preclinical drug testing. To address this need, our interdisciplinary team, consisting of intero biosystems, INC. And the university of michigan, has developed the first stem cell-derived human intestinal organoid (HIO) that contains many of the tissue types found in the native intestine, including the inner lining of the intestine and supporting tissues such as functional smooth muscle that can undergo peristalsis, perfusable blood vessels, and neurons-effectively mimicking the human intestine "in a dish." in this proposal, we will first validate and optimize the HIO system for use in assays for cell viability and cytotoxicity, which are common in the preclinical space. Next, we will develop a model of intestinal fibrosis for drug efficacy testing. Due to the complexity of this HIO model, IT is possible to induce fibrosis with the addition of tgfβ, and a scalable qpcr panel will be developed to assess fibrotic induction. This proposal aims to make significant progress in positioning hios as a powerful microphysiological system that could revolutionize preclinical drug testing.